Table.
Summary of findings
| Vaccine doses, n | Absolute effect*with placebo or no vaccination | Absolute effect*with vaccination (95% CI) | Relative effect†(95% CI) | Timing of outcome measurement | Participants, n | Certainty of the evidence (GRADE) | Interpretation | ||
|---|---|---|---|---|---|---|---|---|---|
| Vaccine effectiveness | |||||||||
| SARS-CoV-2 infection (PCR-confirmed or antigen-test confirmed) | |||||||||
| NRSI | 2 | 20 793 per 100 000 | 8650 per 100 000 (5843 to 10 937) | VE 41·6% (28·1–52·6); VE ratio 0·584 (0·474–0·739) | ≥14 days after second dose to median of 4 months after second dose | >3 376 000‡32, 40, 42, 43, 44, 45, 46, 47 | Low; downgraded by two levels for serious inconsistency (I2=96·6%) | Primary vaccination series probably slightly reduces the risk of SARS-CoV-2 infections with omicron. | |
| NRSI | 3 | 27 595 per 100 000 | 12 418 per 100 000 (11 038 to 13 798) | VE 55% (50–60); VE ratio 0·45 (0·40–0·50) | Up to ≥3 months after third dose | 60 57432 | Moderate; downgraded by one level for serious imprecision (one study only) | Booster vaccination probably reduces the risk of SARS-CoV-2 infections with omicron. | |
| Symptomatic COVID-19 | |||||||||
| NRSI | 2 | 31 326 per 100 000 | 19 203 per 100 000 (15 005 to 24 528) | VE 36·2% (21·5–48·2); VE ratio 0·638 (0·518–0·749) | ≥7 days after second dose to median of 4 months after second dose | 3 262 72732, 45, 48, 49, 50, 51 | Low; downgraded by two levels for serious inconsistency (I2=92·2%) | Primary vaccination series probably slightly reduces the risk of symptomatic COVID-19. | |
| NRSI | 3 | NR§ | NE | VE 61% (55–67); VE ratio 0·39 (0·33–0·45) | Up to ≥3 months after third dose | 60 57432 | Moderate; downgraded by one level for serious imprecision (one study only) | Booster vaccination probably reduces the risk of symptomatic COVID-19. | |
| Hospitalisation due to COVID-19 | |||||||||
| NRSI | 2 | 47 per 100 000¶ | 12 per 100 000 (9 to 15) | VE 75·3% (68·0–81·0); VE ratio 0·25 (0·19–0·32) | ≥7 days after second dose to median of 71 days after second dose | 3 058 48043, 49, 50, 51, 52, 53 | Moderate; downgraded by one level for risk of bias (two studies with a serious risk and four studies with a moderate risk) | Primary vaccination series probably reduces the risk of hospitalisation due to omicron variant-induced COVID-19. | |
| NRSI | 3 | NA | NA | VE NA | NA | 0 | NA | Outcome was not reported in any study. | |
| COVID-19 related mortality | |||||||||
| NRSI | 2 | <1 per 100 000‖ | NE, 0 cases observed | VE NE, 0 cases in vaccinated group, 1 case in control group | Median of 34 days from vaccination to hospitalisation | 2 869 87441, 43, 49, 53 | Low; downgraded by two levels for very serious imprecision (zero or few events) | The evidence is uncertain about the effect of a primary vaccination series on the risk of mortality due to omicron variant-induced COVID-19. | |
| NRSI | 3 | NA | NA | VE NA | NA | 0 | NA | Outcome was not reported in any study. | |
| Multisystem inflammatory syndrome in children | |||||||||
| NRSI | 2 | 18 695 per 100 000** | 4113 per 100 000 (1870 to 9721) | VE 78% (48–90); OR 0·22 (0·10–0·52) | NA | 37454 | Very low; downgraded by one level for serious imprecision (one study only), one level for risk of bias (one study with a serious risk), and one level for serious indirectness (hospitalised cases only) | The evidence is very uncertain about the effect of a primary vaccination series on the risk of PIMS-TS due to infections with omicron. | |
| NRSI | 3 | NA | NA | VE NA | NA | 0 | NA | Outcome was not reported in any study. | |
| Long-term effects of COVID-19 (long COVID or post-COVID-19 condition) | |||||||||
| NRSI | NA | NA | NA | VE NA | NA | 0 | NA | Outcome was not reported in any study. | |
| Vaccine safety | |||||||||
| Serious adverse events | |||||||||
| RCT | 2 | 172 per 100 000 | 143 per 100 000 (36 to 572) | RR 0·83 (0·21–3·33) | Up to median 50–70 days after second dose | 627024, 25 | Low; downgraded by two levels for very serious imprecision (few events and very wide CIs) | The evidence is uncertain about the effect of EMA-approved COVID-19 mRNA vaccines on the risk of serious adverse events. | |
| RCT | 3 | NA | NA | RR NA | NA | 0 | NA | Outcome was not reported in any study. | |
| NRSI | NA | NA | NA | RR NA | NA | 0 | NA | Outcome was not reported in any study. | |
| Adverse events of special interest (myocarditis) | |||||||||
| RCT | 2 | NE, 0 cases observed | NE, 0 cases observed | RR NE, 0 cases observed | Up to median 50–70 days after second dose | 624424, 25 | Low; downgraded by two levels for very serious imprecision (zero events) | The evidence is uncertain about the effect of EMA-approved COVID-19 mRNA vaccines on the risk of myocarditis. | |
| RCT | 3 | NA | NA | RR NA | NA | 0 | NA | Outcome was not reported in any study. | |
| NRSI | 2 | 2 per 100 000 | 10 per 100 000 (0 to 324) | RR 4·6 (0·1–156·1) | 97 days after second dose | 641 57257 | Very low; downgraded by one level for serious indirectness (hospitalised cases only) and two levels for very serious imprecision (few events and very wide CIs) | The evidence is very uncertain about the effect of EMA-approved COVID-19 mRNA vaccines on the risk of myocarditis. | |
| NRSI | 3 | NA | NA | RR NA | NA | 0 | NA | Outcome was not reported in any study. | |
| Reactogenicity, local events (solicited adverse events) | |||||||||
| RCT | 1 | 42 169 per 100 000 | 87 289 per 100 000 (75 904 to 100 000) | RR 2·07 (1·80–2·39) | 7 days after dose | 625924, 25 | Moderate; downgraded by one level for risk of bias (two studies with some concerns of bias) | EMA-approved COVID-19 mRNA vaccines probably increase the risk of local reactions after the first vaccine dose. | |
| RCT | 2 | 42 598 per 100 000 | 87 752 per 100 000 (72 417 to 100 000) | RR 2·06 (1·70–2·49) | 7 days after dose | 619624, 25 | Moderate; downgraded by one level for risk of bias (two studies with some concerns of bias) | EMA-approved COVID-19 mRNA vaccines probably increase the risk of local reactions after the second vaccine dose. | |
| RCT | 3 | NA | NA | RR NA | NA | 0 | NA | Outcome was not reported in any study. | |
| NRSI | NA | NA | NA | RR NA | NA | 0 | NA | Outcome was not reported in any study. | |
| Reactogenicity, systemic events (solicited adverse events) | |||||||||
| RCT | 1 | 48 939 per 100 000 | 53 343 per 100 000 (50 896 to 56 769) | RR 1·09 (1·04–1·16) | 7 days after dose | 625924, 25 | Moderate; downgraded by one level for risk of bias (two studies with some concerns of bias) | EMA-approved COVID-19 mRNA vaccines probably slightly increase the risk of systemic reactions after the first vaccine dose. | |
| RCT | 2 | 44 295 per 100 000 | 65 999 per 100 000 (59 355 to 73 087) | RR 1·49 (1·34–1·65) | 7 days after dose | 619624, 25 | Moderate; downgraded by one level for risk of bias (two studies with some concerns of bias) | EMA-approved COVID-19 mRNA vaccines probably increase the risk of local reactions after the second vaccine dose. | |
| RCT | 3 | NA | NA | RR NA | NA | 0 | NA | Outcome was not reported in any study. | |
| NRSI | NA | NA | NA | RR NA | NA | 0 | NA | Outcome was not reported in any study. | |
| Unsolicited adverse events | |||||||||
| RCT | 2 | 15 072 per 100 000 | 18 237 per 100 000 (16 127 to 20 799) | RR 1·21 (1·07–1·38) | 1 month or 28 days after second dose | 627024, 25 | Moderate; downgraded by one level for risk of bias (two studies with some concerns of bias) | EMA-approved COVID-19 mRNA vaccines probably increase the risk of unsolicited adverse events. | |
| RCT | 3 | NA | NA | RR NA | NA | 0 | NA | Outcome was not reported in any study. | |
| NRSI | NA | NA | NA | RR NA | NA | 0 | NA | Outcome was not reported in any study. | |
EMA=European Medicines Agency. GRADE=Grading of Recommendations, Assessment, Development and Evaluation. NA=not applicable. NE=not estimable. NR=not reported. NRSI=non-randomised study of intervention. PIMS-TS=paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. RCT=randomised controlled trial. RR=risk ratio. VoC=variant of concern.
*
The estimated absolute effect refers to the difference between the observed baseline risk reported for the unvaccinated control group and the risk for experiencing an outcome after vaccination. The absolute effect estimated for the intervention group is based on the relative effect magnitude of an effect and the baseline risk—ie, (observed risk/100 000 unvaccinated children) × relative effect.
†
Relative effects (vaccine effectiveness or RRs were derived from meta-analysis, or from one study if no pooled estimate was available).
‡
Two (25%) of eight studies did not report the number of participants. The studies reporting the number of participants included 3 376 655 children.
§
Crude number of symptomatic COVID-19 cases in unvaccinated children not reported.
¶
Baseline risk was partially driven from case control studies and does not reflect the true incidence risk in this age group.
‖
0 deaths in 1 081 881 vaccinated versus three deaths in 1 787 993 unvaccinated children observed.
**
Hospitalised cases only were included in the analysis; baseline risk was driven by case control studies, thus does not reflect the true incidence risk in age group.